The present invention relates to a method for producing brominated trifluoromethylbenzenes, which can be used as intermediates for medicines and agricultural chemicals.
It is known that an aromatic compound having a bromine atom(s) on its aromatic ring can be obtained by brominating its corresponding aromatic compound. Japanese Patent Unexamined Publication 50-76029 and J. Am. Chem. Soc. Vol. 69, page 947 (1947) disclose a process for producing 3-bromotrifluoromethylbenzene by brominating a trifluoromethylbenzene by bromine in the presence of iron powder or iron chloride. Zh. Org. Ehim. Vol. 27, No. 1, page 125 discloses a process for producing 3bromo-trifluoromethylbenzene by brominating a trifluoromethylbenzene using sulfur tetrafluoride, hydrogen fluoride and bromine. Zh. Prikl. Khim. Vol. 46, No. 9 (1973)page 2012 discloses a process in which 1,3-bis(trifluoromethyl)benzene is simultaneously reacted with chlorine and bromine in the presence of antimony pentachloride, thereby obtaining 3,5-bis(trifluoromethyl)bromobenzene (selectivity: 74.1%) and 3,5-bis(trifluoromethyl)chlorobenzene (selectivity: 24.6%). J. Am. Chem. Soc. Vol, 72 page 1651 (1950) discloses a process in which 1,3-bis(trifluoromethyl)benzene is simultaneously reacted with chlorine and bromine in the presence of a catalytic amount of antimony pentachloride, thereby obtaining 3,5-bis(trifluoromethyl)bromobenzene (conversion: 70%, selectivity: 74.1%). Japanese Patent Unexamined Publication 9-169673 discloses a process in which 1,3-bis(trifluoromethyl)benzene is brominated by N-bromoimide in the presence of a strong acid, thereby obtaining 3,5-bis(trifluoromethyl)bromobenzene.
Bromine is strong in metal corrosiveness. Therefore, bromination is usually conducted in a glass reactor. However, if it is tried to brominate an aromatic compound having a trifluoromethyl group(s), the bromination does not easily occur due to the electron attractive property of the trifluoromethyl group(s). Therefore, it is necessary to make the reaction condition relatively severe to get the bromination. With this, the trifluoromethyl group may be decomposed by Lewis acid catalyst used in the bromination, thereby generating hydrogen fluoride in the reaction system. This hydrogen fluoride tends to corrode glass. Therefore, it has been necessary to avoid using glass as a reactor for conducing the bromination of the above aromatic compound or to conduct such bromination with an extra care using a glass reactor.
Of conventional Lewis acid catalysts, antimony pentachloride is high in reactivity and satisfactory in selectivity. It is, however, high in corrosiveness against metal. Furthermore, antimony compounds are highly soluble in organic matters, resulting in difficulty in separating those from the product. Even if they are separated by washing, it becomes troublesome to treat waste water after the washing.
It is an object of the present invention to provide a process for producing a brominated trifluoromethylbenzene from a trifluoromethylbenzene with high conversion and high selectivity.
According to a first aspect of the present invention, there is provided a first process for producing a brominated trifluoromethylbenzene represented by the general formula (1). The first process comprises brominating in a liquid phase a trifluoromethylbenzene, represented by the general formula (2), by bromine in the presence of an iron containing catalyst under a condition that the bromine is coexistent with chlorine, 
where n is an integer of 1-2, and m is an integer of 1-3 
Where n is an integer of 1-2.
According to a second aspect of the present invention, there is provided a second process for producing a brominated trifluoromethylbenzene represented by the general formula (1). The second process comprises brominating in a gas phase a trifluoromethylbenzene, represented by the general formula (2), by bromine in the presence of a catalyst under a condition that the bromine is coexistent with chlorine.
It is possible to produce a brominated trifluoromethylbenzene represented by the general formula (1) from a trifluoromethylbenzene represented by the general formula (2) with high conversion and high selectivity by both of the first and second processes.
According to the fist process, both selectivity and conversion become high by using an iron-containing catalyst such as an iron halide, particularly iron chloride, since this catalyst has a high activity in the bromination. Furthermore, the catalyst is less soluble in the product. Therefore, the catalyst can easily be separated from the product by a simple operation such as decantation, thereby simplifying the process. The separated catalyst can be used repeatedly in the bromination. Still furthermore, the iron-containing catalyst has a low corrosiveness against metal. With this, the first process can be conducted in a metal reaction vessel. Thus, the first process is a desirable process for producing the brominated trifluoromethylbenzene in an industrial scale.
According to the second process, the bromination is conducted in a gas phase, thereby simplifying the process. Furthermore, the bromination of the second process can proceed efficiently by using a catalyst containing a metal chloride (e.g., iron chloride) carried on a carrier. This catalyst has a high activity and a long lifetime in the bromination. Therefore, it is possible to produce the brominated trifluoromethylbenzene from the trifluoromethylbenzene with high conversion and high selectivity. Thus, the second process has a superior operationability and a high productivity. Furthermore, it is possible to substantially prevent corrosion of a metal reaction vessel, because bromine and chlorine are treated in a vapor phase. Thus, the second process is also a desirable process for producing the brominated trifluoromethylbenzene in an industrial scale.
In the first and second processes, the trifluoromethylbenzene represented by the general formula (1) may be trifluoromethylbenzene, 1,4-bis(trifluoromethly)benzene, 1,3-bis(trifluoromethyl)benzene, or 1,2-bis(trifluoromethyl)benzene, and may be one prepared by any process. For example, Ind. Eng. Chem. 39 [19473] 302 discloses a method for producing 1,3-bis(trifluoromethyl)benzene. This method includes the steps of (a) chlorinating methaxylene to 1,3-bis(trifluoromethyl)benzene and (b) fluorinating the 1,3-bis(trifluoromethyl)benzene by hydrogen fluoride in the absence of catalyst at a temperature of 150-20xc2x0 C. J. Am. Chem. Soc. 71 [1949] 1490 discloses the same method except that the step (b) is conducted in the presence of antimony pentachloride catalyst at room temperature.
In the first and second processes, the amount of bromine used may vary depending on the amount of the brominated trifluoromethylbenzene to be produced, and is 0.5 m (m is an integer of 1-3 in the general formula (1)) moles or more for each m number. In order to produce a monobromtrifluoromethylbenzene, the amount of bromine can be 0.5 moles or more, preferably 0.5-2 moles, more preferably 0.5-1 mole, still more preferably 0.5-0.75 moles, per mole of the trifluoromethylbenzene. Alternatively, the amount of bromine can be 0.5 moles or less per mole of the trifluoromethylbenzene in order to suppress the production of polybrominated compounds generated in the course of the complete bromination of the trifluoromethylbenzene.
In the first process, chlorine is used in an amount of 1 mole or more per mole of bromine. In fact, it suffices to use 1 to about 2 moles of chlorine per mole of bromine. Furthermore, it can be adjusted to 1 to about 1.2 moles by suitably controlling the reaction. If the amount of chlorine is less than 1 mole, conversion of bromine may become too low. If chlorine is used too much, it may cause the production of chlorinated trifluoromethylbenzenes and may lower the yield of the brominated trifluoromethylbenzene. Furthermore, it makes difficult to treat chlorine during the reaction.
In the first process, although the total amount of chlorine can be put into a reactor at one time, it is preferable to add chlorine to the reactor continuously or intermittently. In fact, it is preferable that bromine in the reaction system is always in excess of chlorine in order to suppress the formation of chlorinated compounds as by-products. Therefore, it is preferable to add chlorine gradually as the reaction proceeds. In case that the reaction pressure is maintained constant by purging hydrogen chloride formed in the reaction, it is possible to reduce the loss of the unreacted chlorine and bromine chloride by returning them to the reactor using a reflux condenser connected to the exit of the reactor. When chlorine is added, it is optional to use a suitable apparatus for accelerating the gas-solid contact, such as stirrer, bubbling pipe, sparger, or the like.
In the first process, the iron-containing catalyst may be an iron halide. The catalyst may be in the form of metallic iron or an iron-containing alloy or compound when a reactor is charged with the catalyst, as long as the catalyst is in the form of halide during the reaction. In fact, the catalyst is preferably ferric chloride, ferric bromide or the like, which is easily available. Iron contained in the catalyst is in an amount of preferably 0.1-100 moles, more preferably 1-50 moles, still more preferably 5-30 moles, per 100 moles of the trifluoromethylbenzene. If it is less than 0.1 moles, the reaction rate may become too low. Even if it is greater than 100 moles, the reaction proceeds with no problem. With this, however, the reaction rate and the yield do not improve further, and the operation becomes cumbersome.
In the first process, an inert solvent may be used. Such solvent is not particularly limited and may be one of chlorine-containing solvents such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, tetrachloroethane, pentachloroethane, trichloroethylene, and tetrachloroethylene.
In the first process, the reaction temperature may vary depending on the types of the raw material and the product. In fact, it may be in a range of about 50-200xc2x0 C., preferably 90-150xc2x0 C., more preferably 100-130xc2x0 C. If it is lower than 50xc2x0 C., the reaction may become too slow. If it is higher than 200xc2x0 C., the selectivity may become too low. In particular, the reaction temperature is preferably 150xc2x0 C. or lower in order to obtain monobromotrifluoromethylbenzene. The pressure of the reactor may be in a range of 1-100 kg/cm2 (0.1-10 MPa), preferably 6-50 kg/cm2 (0.6-5 MPa). The reactor may be made of metal such as stainless steel, Hastelloy, or Monel metal.
When a monobromotrifluoromethylbenzene is produced by intermittently adding chlorine, the first process may be conducted as follows. At first, the reactor is charged with predetermined amounts of the trifluoromethylbenzene, bromine and an iron halide and an arbitrary amount of chlorine (for example, one tenth of the total amount of chlorine necessary to complete the reaction). Then, the temperature of the reaction liquid is increased to a predetermined temperature with stirring. As the reaction proceeds, the remainder of chlorine is bubbled into the reaction liquid a little at a time. The reaction pressure is maintained constant by suitably purging hydrogen chloride formed in the reaction. The reaction is continued in this manner until the composition of the product becomes a desired one. After the reaction, the stirring is stopped to allow the reaction liquid to stand still, thereby precipitating the iron halide. After that, the supernatant liquid is taken out, thereby leaving a most part of the iron halide in the reactor. Such iron halide left in the reactor can be repeatedly used as the catalyst.
In the first and second processes, the brominated trifluoromethylbenzene represented by the general formula (1) is a brominated compound prepared by replacing xe2x80x9cmxe2x80x9d (i.e., an integer of 1-3 as defined in the general formula (1)) of the hydrogen atom(s) on the benzene ring of the trifluoromethylbenzene with the corresponding number of bromine atoms, with no change of the trifluoromethyl group(s). In fact, the preferential position of the hydrogen atom to be replaced with bromine atom depends on the type of the trifluoromethylbenzene. For example, it is possible to obtain as a main product of the bromination 3-bromo-trifluoromethylbenzene from trifluoromethylbenzene, 3,5-bis(trifluoromethyl)bromobenzene from 1,3-bis(trifluoromethyl)benzene, 2,5-bis(trifluoromethyl)bromobenzene from 1,4-bis(trifluoromethyl)benzene, or 3,4-bis(trifluoromethyl)bromobenzene from 1,2-bis(trifluoromethyl)benzene.
In the first process, the reaction product taken out of the reactor can be purified by one of various methods. The reaction liquid may contain bromine, chlorine and an iron halide besides organic matters containing the target product. This iron halide can be removed as an insoluble faction by decantation or filtration. The other unnecessary components can easily be removed by washing with a sodium sulfite aqueous solution and then a sodium hydroxide aqueous solution or by fash distillation, thereby obtaining a crude product of the brominated trifluoromethylbenzene, which is free of bromine, chlorine and the iron halide. This crude product can be purified by distillation to obtain the brominated trifluoromethylbenzene with high purity. This brominated trifluoromethylbenzene can be used as a raw material of various reactions. For example, it can be turned into bis(trifluoromethyl)benzoic acid or bis(fluoromethyl)benzoate, bis(trifluoromethyl)benzamide and the like by reactions with carbon monoxide in a liquid or gas phase in the presence of a catalyst containing a metal (e.g., palladium) as an activated species.
In the second process, the catalyst is preferably one in which a metal chloride is carried on a carrier. Examples of this carrier are activated carbon, alumina, silica, titania, aluminum fluoride, zirconia, Molecular Sieve, and fluororesins. Of these, activated carbon and titania are preferable, and activated carbon is particularly preferable. The activated carbon is not limited to a particular type. The activated carbon may be prepared from a vegetable raw material such as wood, charcoal, coconut husk coal, palm core coal, or raw ash; a coal such as peat, lignite, brown coal, bituminous coal, or anthracite; a petroleum raw material such as petroleum residue or oil carbon; or a synthetic resin raw material such as carbonated polyvinylidene chloride. The activated carbon may be selected from various commercial activated carbons. Examples of commercial activated carbons that are usable in the second process are activated carbons made of bituminous coal, such as BPL GRANULAR ACTIVATED CARBON (trade name) of TOYO CALGON CO. and 3GX (trade name) of KURARAY CHEMICAL CO., LTD., and coconut husk coals, such as GRANULAR SHIRO SAGI GX, CX and XRC (trade names) of Takeda Chemical Industries, Ltd. and PCB (trade name) of TOYO CALGON CO. An activated carbon used in the second process is generally in the form of granules. Furthermore, it may be in the form of sphere, fiber, powder or honeycomb. Its shape and size are not particularly limited, and may be decided depending on the reactor. As mentioned above, the catalyst preferably contains a metal chloride carried on the carrier. This metal chloride contains at least one metal selected from iron, copper, nickel, cobalt, zinc, titanium, aluminum, tantalum, palladium, potassium and the like. Of these, iron, tantalum and titanium are preferable, and iron is the most preferable. It is also preferable to use iron and at least one other metal together. In this case, the molar ratio of iron to the at least one other metal is preferably within a range of 50/50 to 100/0. The method for preparing the catalyst used in the second process is not particularly limited. It can be prepared by immersing carrier in a solution of at least one metal compound or by spraying such solution on carrier. The metal compound carried on the carrier is in an amount of preferably from 0.01 to 100 parts by weight, more preferably from 1 to 50 parts by weight, per 100 parts by weight of the carrier. If it is less than 0.01 parts by weight, conversion may become too low. If it is greater than 100 parts by weight, the metal compound may not stably be carried on the carrier. The metal compound is preferably one soluble in a solvent (e.g., water, ethanol and acetone), such as chloride or bromide. Specific examples of the metal compound are iron chloride (ferric chloride or ferrous chloride), iron bromide, copper chloride, nickel chloride, cobalt chloride, zinc chloride, titanium chloride, aluminum chloride, tantalum chloride, palladium chloride, and potassium chloride. It is assumed that a metal bromide carried on the carrier turns into a metal chloride in the bromination. Therefore, either metal chloride or metal bromide can be used for the catalyst.
In the second process, the reaction is conducted at a temperature of preferably from 90 to 300xc2x0 C., more preferably from 100 to 200xc2x0 C., still more preferably from 110 to 150xc2x0 C. If it is lower than 90xc2x0 C., conversion may become too low. If it is higher than 300xc2x0 C., selectivity of the target product may become too low due to the formation of polybrominated compounds. The reaction pressure does basically not have an influence on the reaction. Thus, it is not particularly limited so long as it is adjusted to being in a range where the raw materials, intermediates and the product do not liquefy. The reaction pressure can be in a range of 0.1-1 MPa. The reaction may be conducted at about normal pressure (atmospheric pressure) or under a little pressurized or reduced condition. The contact time may be in a range of 0.1 to 300 seconds, preferably 5 to 60 seconds.
In the second process, chlorine may be used in an amount of from about 0.7 moles to about 1.5 moles, per mole of bromine. In fact, it suffices to use about 0.8 to about 1.2 moles of chlorine per mole of bromine. Furthermore, it can be adjusted to about 0.9 to about 1.1 moles by suitably controlling the reaction. If the amount of chlorine is less than 0.7 moles, selectivity of the brominated trifluoromethylbenzene becomes high. With this, however, conversion of bromine may become too low. If it is greater than 1.5 moles, it may cause the production of chlorinated trifluoromethylbenzenes and may lower the selectivity of the brominated trifluoromethylbenzene. Furthermore, it makes difficult to treat chlorine during the reaction.
In the second process, it is optional to previously mix bromine with the trifluoromethylbenzene and introduce the resulting mixture into the reactor. Alternatively, they may be separately introduced into the reactor. Similarly, it is optional to previously mix chlorine with bromine and introduce the resulting mixture into the reactor. Alternatively, they may be separately introduced into the reactor. It is also preferable to vaporize such mixture before it is introduced into the reactor.
In the second process, the reactor may be made of a material (e.g., stainless steel, Hastelloy, Monel metal and platinum) so long as it has heat resistance and corrosion resistance against hydrogen fluoride, hydrogen chloride, chlorine, bromine, hydrogen bromide and the like. Furthermore, the reactor may be lined with such material. Although bromine having a tendency to corrode metal is used in the second process, corrosion of the inside of the reactor does almost not occur for a long time.
In the second process, the reaction gas containing the brominated trifluoromethylbenzene, which flows out of the reactor, can be purified by a known method to produce a product. In this purification, bromine, chlorine, bromine chloride and hydrogen chloride contained in the reaction gas can easily be removed by (1) combining a reducing agent (e.g., sodium sulfite) and a basic material (e.g., sodium hydroxide, potassium hydroxide, and calcium hydroxide) for neutralizing the acid components or by (2) flash distillation. The collected bromine in the purification can be used again in the bromination. The crude product obtained by the above purification can be turned into the brominated trifluoromethylbenzene with high purity by distillation.
When it is intended to produce a monobromotrifluoromethylbenzene under atmospheric pressure, the second process may be conducted as follows. At first, a reaction tube is charged with a predetermined amount of a catalyst (i.e., activated carbon carrying thereon iron chloride), followed by heating to a predetermined temperature. After that, predetermined amounts of the trifluoromethylbenzene, bromine and chlorine are introduced into the reaction tube, thereby conducting the reaction. The crude product collected in a receiver is purified by (1) washing with a sodium sulfite aqueous solution and then a sodium hydroxide aqueous solution or by (2) flash distillation, followed by distillation to obtain a brominated trifluoromethylbenzene with high purity. Bromine collected by flash distillation can be used again in the reaction.